The definition of osmosis is the

Passive Water Reabsorption by Osmosis Coupled Mainly to Sodium Reabsorption

When solutes are transported out of the tubule by primary or secondary active transport, their concentrations tend to decrease inside the tubule while increasing in the renal interstitium. This phenomenon creates a concentration difference that causes osmosis of water in thesame direction that the solutes are transported, from the tubular lumen to the renal interstitium. Some parts of the renal tubule, especially the proximal tubule, are highly permeable to water, and water reabsorption occurs so rapidly that there is only a small concentration gradient for solutes across the tubular membrane.

A large part of the osmotic flow of water in the proximal tubules occurs through water channels(aquaporins) in the cell membranes, as well as through thetight junctions between the epithelial cells. As noted previously, the junctions between the cells are not as tight as their name would imply and permit significant diffusion of water and small ions. This condition is especially true in the proximal tubules, which have a high permeability for water and a smaller but significant permeability to most ions, such as sodium, chloride, potassium, calcium, and magnesium.

Water moving across the tight junctions by osmosis also carries with it some of the solutes, a process referred to assolvent drag. In addition, because the reabsorption of water, organic solutes, and ions is coupled to sodium reabsorption, changes in sodium reabsorption significantly influence the reabsorption of water and many other solutes.

In the more distal parts of the nephron, beginning in the loop of Henle and extending through the collecting tubule, the tight junctions become far less permeable to water and solutes, and the epithelial cells also have a greatly decreased membrane surface area. Therefore, water cannot move easily across the tight junctions of the tubular membrane by osmosis. However, antidiuretic hormone (ADH) greatly increases the water permeability in the distal and collecting tubules.

Thus, water movement across the tubular epithelium can occur only if the membrane is permeable to water, no matter how large the osmotic gradient. In the proximal tubule and descending loop of Henle, water permeability is always high, and water is rapidly reabsorbed to reach osmotic equilibrium with the surrounding interstitial fluid. This high permeability is due to abundant expression of the water channelaquaporin-1 (AQP-1) in the luminal and basolateral membranes. In the ascending loop of Henle, water permeability is always low, so almost no water is reabsorbed, despite a large osmotic gradient. Water permeability in the last parts of the tubules—the distal tubules, collecting tubules, and collecting ducts—occurs through aquaporins and can be high or low, depending on the presence or absence of ADH.

1.2 Osmosis

Osmosis is a special type of diffusion, namely the diffusion of water across a semipermeable membrane. Water readily crosses a membrane down its potential gradient from high to low potential (Fig. 19.3) [4]. Osmotic pressure is the force required to prevent water movement across the semipermeable membrane. Net water movement continues until its potential reaches zero. An early application of the basic principles of osmosis came from the pioneering work on hemolysis of red blood cells by William Hewson in the 1770s (see Chapter 2). It has also been discussed that MLVs (multilamellar vesicles, liposomes) behave as almost perfect osmometers, swelling in hypotonic solutions and shrinking in hypertonic solutions (see Chapter 3) [5,6]. Liposome swelling and shrinking can be easily followed by changes in absorbance due to light scattering using a simple spectrophotometer. Therefore, osmosis has been investigated for many years using common and inexpensive methodologies and a lot is known about the process.

Membranes are rarely, if ever, perfectly semipermeable. Deviation from ideality is defined by a reflection coefficient (σ). For an ideal semipermeable membrane where a solute is totally impermeable, σ = 1. If a solute is totally permeable (its permeability is equal to water), σ = 0. Biological membranes are excellent semipermeable barriers with σ = 0.75 to 1.0.

The MCD produces a concentrated urine by osmosis, driven by the osmotic gradient between the medullary interstitium and the lumen

Whereas the loop of Henle acts as acountercurrent multiplier and the loop-shaped vasa recta act as acountercurrent exchanger, the MCD acts as an unlooped orstraight-tube exchanger. The wall of the MCD has three important permeability properties: (1) in the absence of AVP, it is relatively impermeable to water, urea, and NaCl along its entire length; (2) AVP increases its water permeability along its entire length; and (3) AVP increases its urea permeability along just the terminal portion of the tube (IMCD). The collecting duct traverses a medullary interstitium that has a stratified, ever-increasing osmolality from the cortex to the tip of the papilla. Thus, along the entire length of the tubule, the osmotic gradient across the collecting-duct epithelium favors the reabsorption of water from lumen to interstitium.

A complicating factor is that two solutes—NaCl and urea—contribute to the osmotic gradient across the tubule wall. As fluid in the collecting-duct lumen moves from the corticomedullary junction to the papillary tip, the [NaCl] gradient across the tubule wall always favors the osmotic reabsorption of water (Fig. 38-7). For urea, the situation is just the opposite. However, because the ICT, CCT, and OMCD are all relatively impermeable to urea, water reabsorption predominates in the presence of AVP and gradually causes luminal [urea] to increase in these segments. Because the interstitial [urea] is low in the cortex, a rising luminal [urea] in the ICT and CCTopposes water reabsorption in these segments. Even when the tubule crosses the corticomedullary junction, courses toward the papilla, and is surrounded by interstitial fluid with an ever-increasing [urea], the transepithelial urea gradient still favors water movement into the lumen, which is a handicap for the osmotic concentration of the tubule fluid.

The IMCD partially compensates for this problem by acquiring, in response to AVP, a high permeability to urea. The result is a relatively low reflection coefficient for urea (σurea; seep. 468), which converts any transepithelial difference in [urea] into a smaller difference in effective osmotic pressure (seepp. 132–133). Thus, water reabsorption continues from the IMCD even though [urea] in tubule fluid exceeds that in the interstitium. The combination of a high interstitial [NaCl] and high σNaCl (σNaCl = 1.0), along with a low σurea (σurea = 0.74), promotes NaCl-driven waterreabsorption. The high AVP-induced urea permeability has the additional effect of raising interstitial [urea], which further reduces the adverse effect of the high luminal [urea] on water reabsorption.

If luminal urea opposes the formation of a concentrated urine, why did the mammalian kidney evolve to have high levels of urea in the lumen of the collecting tubules and ducts? At least two reasons are apparent. First, because urea is the body's major excretable nitrogenous waste, the kidney's ability to achieve high urinary [urea] reduces the necessity to excrete large volumes of water to excrete nitrogenous waste. Second, as we have already seen, the kidney actually takes advantage of urea—indirectly—to generate maximally concentrated urine. In the presence of AVP, the permeability of the IMCD to urea is high, so that large amounts of urea can enter the medullary interstitium. The high interstitial [urea] energizes the increase in luminal [NaCl] in the tDLH, which, in turn, fuels the single effect in the tALH, thus creating the high inner-medullary [NaCl] that isdirectly responsible for concentrating the urine.

IIIA. Definition of Osmosis

Osmosis refers to the movement of fluid across a membrane in response to differing concentrations of solutes on the two sides of the membrane. Osmosis has been used since antiquity to preserve foods by dehydration with salt or sugar. The removal of water from a tissue by salt was referred to as imbibition. This description comes from the notion that these solutes attracted water from material they touched. In 1748, J.A. Nollet used an animal bladder to separate chambers containing water and wine. He noted that the volume in the wine chamber increased and, if this chamber was closed, a pressure developed. He named the phenomenon osmosis from the Greek ωσμoς, meaning thrust or impulse.

Pfeffer (1877) provided early quantitative observations on osmosis. He made an artificial membrane in the walls of an unglazed porcelain vessel by reacting copper salts with potassium ferrocyanide to form a copper ferrocyanide precipitation membrane on the surface of the vessel. He used this membrane to separate a sucrose solution inside the vessel from water outside and found a volume flow from the water side to the sucrose side. Pfeffer observed that the flow was proportional to the sucrose concentration. Further, a pressure applied inside the vessel produced a filtration flow proportional to the pressure. He found that a closed vessel containing a sucrose solution would develop a pressure proportional to the concentration of sucrose. He recognized this as an equilibrium state in which the pressure balanced the osmosis caused by the sucrose solution. Pfeffer’s original data for the osmotic pressure of sucrose solutions are plotted in Fig. 16.2. He defined osmotic pressure as the hydrostatic pressure necessary to stop osmotic flow across a barrier (e.g. a membrane) that is impermeable to the solute. This concept is illustrated in Fig. 16.3. Osmotic pressure is a property intrinsic to the solution and is measured at equilibrium, when the pressure-driven flow exactly balances the osmotic-driven flow. By defining osmotic pressure in this way, we assign a positive value to an apparent reduction in pressure brought about by dissolving the solute. Thus, fluid movement occurs from the solution of low osmotic pressure (water) to the solution of high osmotic pressure, opposite in direction to the hydraulic flow of water from high to low hydrostatic pressure.

An ideal semipermeable membrane is required for determining osmotic pressure. These membranes are permeable to water but absolutely impermeable to solute. The concept of osmotic pressure differs from tonicity in that tonicity compares two solutions separated by a specific non-ideal membrane. If the membrane is highly permeable to solute as well as to water, no water flow will occur and, therefore, the externally applied pressure required to stop osmosis is zero. This observation makes it plain that the effective osmotic pressure, which is measured with a real membrane, must be due to some interaction of the membrane with the solute because pressure depends on both the specific solute and the specific membrane.

Summary

Osmosis refers to the movement of fluid across a membrane in response to different concentrations of solutes on the two sides of the membrane. The movement of fluid is toward the more concentrated solution. Osmotic pressure is defined as the pressure that must be applied to the solution side to stop fluid movement when a semipermeable membrane separates a solution from pure water. Here, the semipermeable membrane is permeable to water but not to solute. The osmotic pressure for dilute ideal solutions obeys van’t Hoff’s Law:

π=RTΣCs

which can be derived on thermodynamic grounds. Because the solutions are not ideal, the equation is refined by including an osmotic coefficient, φs, characteristic of each solute:

πobserved=RTΣφsCs

Defined in this way, the osmotic pressure is a pressure deficit caused by dissolving solutes. However, membranes that are somewhat permeable to the solute develop a transient osmotic pressure that is less than that predicted by van’t Hoff’s Law. Thus the actual pressure developed across a membrane that separates a solution from pure water depends on the interaction of the solute with the membrane. The correction for partially permeable membranes requires the reflection coefficient, σ:

πobserved=RTΣσsφsCs

The magnitude of the pressure tells us nothing of the flow. Osmotic pressure and hydrostatic pressure add to drive fluid flow across the membrane, with a proportionality constant, Lp. The phenomenological equation describing fluid flow is

Qv=ALp(ΔP−σΔπ)

Osmosis and osmotic pressure is a thermodynamic concept which exists independently of mechanism. In microporous membranes, osmosis is caused by a momentum deficit within the pores due to the reflection of solute molecules by the membrane. This reduces the pressure on the solution side of the pore by π for a semipermeable membrane.

Thus there are three characteristic parameters for describing passive material transfer across membranes: the permeability, p, the hydraulic conductivity, Lp, and the reflection coefficient, σ.

Osmolarity is a kind of concentration measure, distinct from molarity. It is related to other colligative properties of solutions including freezing point depression, vapor pressure depression, and boiling point elevation. Tonicity is a related concept but involves a real, biological membrane that may not be semipermeable. Tonicity makes reference to a particular cell and its membrane. Solutions may be isoosmotic but not isotonic.

Cells respond to swelling or shrinking according to the empirical relation:

V/V0=(1−Vb/V0)πisotonic/π+Vb/V0

where V0 is the volume of the cell under isotonic conditions. Vb is interpreted as the osmotically inactive volume. If Vb=0, the cell would behave like an ideal osmometer.

4.23.3.10.2 Osmotic tablets

Osmosis can be defined as the spontaneous movement of solvent molecules through a semi-permeable membrane from a lower-concentration solution to a higher-concentration solution. An osmotic pump can be created inside a tablet using osmosis to “push” the drug out at a constant rate independent of drug concentration. The driving force behind this mechanism is the osmotic pressure between the inside of the dosage form and the bulk media created by an osmotically active excipient and drug. The movement of solvent can then be regulated using semipermeable polymeric excipients. Drug dissolution is then controlled by limiting the amount of water flowing into the tablet by which the dissolved drug is released at a constant rate through a hole in the membrane created with a laser. The first type of tablets using this technology were named Osmotic Release Oral System (OROS), and consisted of a solid tablet core surrounded by a rate controlling semi-permeable coating and a drug releasing orifice.

A more complex osmotic tablet design is the push-pull pump. The basic design starts with a bilayer tablet where one layer contains the drug and the other layer is made of an osmotically active agent (e.g., salt) and swellable polymer that acts as the push compartment. As before, the entire tablet is coated with a semipermeable membrane with the laser-drilled hole being made on the drug containing side. After administration, the tablet interior will be filled with gastric fluid that in turn hydrates and swells the polymer of the push layer. This causes the dissolved drug to be pushed out of the open orifice. An example of such a tablet is the product Procardia XL, composed of an osmotically active drug core of nifedipine and an external semipermeable coating of cellulose acetate. The insoluble cellulose acetate coating controls the drug release by limiting the rate at which solvent is able to enter the tablet interior and push the drug out through the laser-formed hole in the coating.75 With sulfonylurea glipizide (Glucotrol XL),76 the push layer is made of water swellable PEO and sodium chloride that acts as the osmotic agent. The semipermeable coating consists of EC and PEG. Since the PEG is water soluble, the higher the amount contained in the membrane the more porous the membrane will be, leading to faster drug release rates.

15.4.1.3 Osmotic pump systems

Osmosis, the natural movement of water into a solution through a semipermeable membrane, has been employed in the development of zero-order release drug delivery systems (Fig. 15.3). Only water, not solutes, can diffuse through the semipermeable membrane (Herbig et al., 1995). For different polymeric membranes, their water vapor transmission value is distinguishable, and the selection of a semipermeable membrane depends on the nature of application. The rate of release of drug from these products is determined by the constant flow of water across a semipermeable membrane into a reservoir that contains an osmotic agent called as osmogen. The rate of release is constant and can be controlled within fixed limits, yielding relatively constant drug concentration. The osmotic pump is similar to a reservoir device but it contains an osmogen. Osmogen is the active agent in salt form, which acts to imbibe water from the surrounding medium through a semipermeable membrane (Gupta et al., 2011). Pressure is developed within the reservoir which forces the active agent out of the reservoir device through an orifice. The rate of release can be adjusted by changing the osmogen and size of the orifice. The constant release is unaffected by the environment of the gastrointestinal tract and relying simply on the passage of water into the dosage form, acts as an advantage for this type of system (Lachman et al., 1991). Consequently, osmotically controlled systems can be classified in to single chamber osmotic pump (elementary osmotic pump) and multichamber osmotic pump (push-pull osmotic pump, osmotic pump with nonexpanding chamber) (Fig. 15.3). Specific types: are controlled porosity osmotic pump, monolithic bursting osmotic pump, osmotic bursting osmotic pump, osmotic release oral system-colon targeted (OROS-CT), multiparticulate delayed release systems, and liquid oral osmotic system (Vyas and Khar, 2000; Bechgaard and Nielson, 1978).

Definitions

Osmosis: This is the hydrostatic force acting to equalize the concentration of water on both sides of the membrane that is impermeable to substances dissolved in that water. Water will move along its concentration gradient. This force is termed osmotic pressure or, in the case of colloids, e.g., albumin, oncotic pressure. It is proportional to the number of atoms/ions/molecules in solution and is expressed as mOsm/liter (osmolarity) or mOsm/kg (osmolality) of solution. The cell membrane and the capillary membrane are both partially permeable membranes, although not strictly semipermeable in the chemical sense. They act, however, as partial barriers dividing the ECF from the ICF space, and the intravascular from the interstitial space. Osmotic or oncotic shifts occur across these membranes, modified by physiological as well as pathological mechanisms.

Osmolarity describes the molar number of osmotically active particles per liter of solution. In practice, the osmolarity of a solution can be “calculated” by adding up the milliequivalent concentrations of the various ions in the solution.

Osmolality describes the molar number of osmotically active particles per kilogram of solvent. This value is directly “measured” by determining either the freezing point or the vapor pressure of the solution. For most dilute salt solutions, osmolality is equal to or slightly less than osmolarity (Box 49.2).

Box 49.2

Calculation of the Osmolarity of 0.9% Saline

The molecular weight of NaCl is 58.43

0.9% NaCl contains 9 g NaCl/1000 mL solution

Molarity of 0.9% solution = 9 g/L/58.43 g/mol = 0.154 mol/L or a 154 mmol/L solution of NaCl

Since each molecule of NaCl dissociates into Na+ and Cl− ions

Molar value is multiplied by 2 = 308 = osmolarity of 0.9% saline.

Colloid osmotic pressure: Osmolarity/osmolality is determined by the total number of dissolved “particles” in a solution, regardless of their size. Colloid osmotic pressure is the osmotic pressure generated by large molecules (e.g., albumin, hetastarch, dextran).

The colloid osmotic pressure becomes particularly important in biological systems where vascular membranes are often permeable to small ions, but not to large molecules (Box 49.3).

Box 49.3

Calculation of Osmotic Pressure

Osmotic pressure π = CRT

C = 0.001 mmol/L

R = 0.08206

T = 273K+36K = 309K(body temperature)

Hence π = CRT = (0.001)(0.08206)(309°)° = 0.02535 atm or 19.27 mmHg

Hemodilution: The beneficial effects of hemodilution are based on the correlation of hematocrit and whole blood viscosity. As the hematocrit and viscosity decrease, the cerebrovascular resistance correspondingly decreases and cerebral blood flow increases. However, one argument against hemodilution is that the oxygen carrying capacity of the blood also decreases. However, experimental evidence suggests that a hematocrit of 33% provides an optimal balance between viscosity and oxygen carrying capacity, and this has been applied clinically.

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